title: Effects of anesthesia and species on the uptake or binding of radioligands in vivo in the Göttingen minipig.
abstract: Progress in neuroscience research often involves animals, as no adequate alternatives exist to animal models of living systems. However, both the physiological characteristics of the species used and the effects of anesthesia raise questions of common concern. Here, we demonstrate the confounding influences of these effects on tracer binding in positron emission tomography (PET). We determined the effects of two routinely used anesthetics (isoflurane and propofol) on the binding of two tracers of monoamine function, [(11)C]SCH23390, a tracer of the dopamine D1 and D5 receptors, and the alpha2-adrenoceptor antagonist, [(11)C]yohimbine, in Göttingen minipigs. The kinetics of SCH23390 in the pigs differed from those of our earlier studies in primates. With two different graphical analyses of uptake of SCH23390, the initial clearance values of this tracer were higher with isoflurane than with propofol anesthesia, indicative of differences in blood flow, whereas no significant differences were observed for the volumes of distribution of yohimbine. The study underscores the importance of differences of anesthesia and species when the properties of radioligands are evaluated under different circumstances that may affect blood flow and tracer uptake. These differences must be considered in the choice of a particular animal species and mode of anesthesia for a particular application.
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Nørrebrogade 44, Building 10G, 6th Floor, 8000 Aarhus, Denmark.
authors.forename: Aage K O
authors.initials: AK
authors.lastname: Alstrup
authors.forename: Anne M
authors.initials: AM
authors.lastname: Landau
authors.forename: James E
authors.initials: JE
authors.lastname: Holden
authors.forename: Steen
authors.initials: S
authors.lastname: Jakobsen
authors.forename: Anna C
authors.initials: AC
authors.lastname: Schacht
authors.forename: Helene
authors.initials: H
authors.lastname: Audrain
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.forename: Axel K
authors.initials: AK
authors.lastname: Hansen
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.forename: Doris J
authors.initials: DJ
authors.lastname: Doudet
mesh_terms: D000758:Anesthesia; D000818:Animals; D001552:Benzazepines / Q000493:pharmacokinetics; D005260:Female; D008024:Ligands; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature / Q000378:metabolism*; D013997:Time Factors; D015016:Yohimbine / Q000493:pharmacokinetics
chemical_list: D001552:Benzazepines; D008024:Ligands; D019275:Radiopharmaceuticals; C534628:SCH 23390; D015016:Yohimbine